Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 4528906, 11 pages
http://dx.doi.org/10.1155/2016/4528906
Research Article

Targeting Pin1 Protects Mouse Cardiomyocytes from High-Dose Alcohol-Induced Apoptosis

1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
2Department of Inpatient Abdominal Ultrasonography, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
3Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China

Received 16 June 2015; Revised 19 August 2015; Accepted 23 August 2015

Academic Editor: Rakesh K. Singh

Copyright © 2016 Yuehong Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Long-term heavy alcohol consumption is considered to be one of the main causes of left ventricular dysfunction in alcoholic cardiomyopathy (ACM). As previously suggested, high-dose alcohol induces oxidation stress and apoptosis of cardiomyocytes. However, the underlying mechanisms are yet to be elucidated. In this study, we found that high-dose alcohol treatment stimulated expression and activity of Pin1 in mouse primary cardiomyocytes. While siRNA-mediated knockdown of Pin1 suppressed alcohol-induced mouse cardiomyocyte apoptosis, overexpression of Pin1 further upregulated the numbers of apoptotic mouse cardiomyocytes. We further demonstrated that Pin1 promotes mitochondria oxidative stress and loss of mitochondrial membrane potential but suppresses endothelial nitric oxide synthase (eNOS) expression in the presence of alcohol. Taken together, our results revealed a pivotal role of Pin1 in regulation of alcohol-induced mouse cardiomyocytes apoptosis by promoting reactive oxygen species (ROS) accumulation and repressing eNOS expression, which could be potential therapeutic targets for ACM.